X Xu1,2, L Wu3, Z Q Lu1, P Xia1,2, X P Zhu1,2, X Gao4,5. 1. Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of Fudan University, NO. 180, Feng Lin Road, Xu Hui District, Shanghai, 200032, People's Republic of China. 2. Institute of Chronic Metabolic Diseases of Fudan University, NO. 130, Dong An Road, Xu Hui District, Shanghai, 200032, People's Republic of China. 3. Department of Geriatrics, Affiliated Zhongshan Hospital of Fudan University, Shanghai, 200032, People's Republic of China. 4. Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of Fudan University, NO. 180, Feng Lin Road, Xu Hui District, Shanghai, 200032, People's Republic of China. gao.xin@zs-hospital.sh.cn. 5. Institute of Chronic Metabolic Diseases of Fudan University, NO. 130, Dong An Road, Xu Hui District, Shanghai, 200032, People's Republic of China. gao.xin@zs-hospital.sh.cn.
Abstract
PURPOSES: Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats. METHODS: SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose. The non-radioactive microsphere technique was adopted to measure the organ blood flow. Nitric oxide synthase (NOS) blocker L-NAME was used to address whether NO was involved in mediating the vasoactive effects of TMPP. RESULTS: In the TMPP group, TMPP increased the PBF (pancreatic blood flow), IBF (islet blood flow), and fIBF (fraction of islet blood flow out of pancreatic blood flow) by 57, 76 and 47%, respectively, after 30% glucose infusion, compared with the control, indicating that TMPP could regulate islet microcirculation. Furthermore, TMPP induced a 66% elevation of IBF and 37% of fIBF in the 30% glucose subgroups than the 15% ones. In 30% glucose-treated subgroups, TMPP improved the blood glucose concentration by 10%, compared with the control (19.3 ± 0.64 vs 17.32 ± 0.56 mmol/l, P < 0.05), without influencing the insulin secretion. Blocking NO formation prevented the enhanced PBF and IBF, evoking by TMPP with 30% glucose. CONCLUSIONS: TMPP can regulate the pancreatic islet microcirculation and possess a hypoglycemia effect after glucose infusion through affecting the islet microcirculation.
PURPOSES: Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats. METHODS: SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose. The non-radioactive microsphere technique was adopted to measure the organ blood flow. Nitric oxide synthase (NOS) blocker L-NAME was used to address whether NO was involved in mediating the vasoactive effects of TMPP. RESULTS: In the TMPP group, TMPP increased the PBF (pancreatic blood flow), IBF (islet blood flow), and fIBF (fraction of islet blood flow out of pancreatic blood flow) by 57, 76 and 47%, respectively, after 30% glucose infusion, compared with the control, indicating that TMPP could regulate islet microcirculation. Furthermore, TMPP induced a 66% elevation of IBF and 37% of fIBF in the 30% glucose subgroups than the 15% ones. In 30% glucose-treated subgroups, TMPP improved the blood glucose concentration by 10%, compared with the control (19.3 ± 0.64 vs 17.32 ± 0.56 mmol/l, P < 0.05), without influencing the insulin secretion. Blocking NO formation prevented the enhanced PBF and IBF, evoking by TMPP with 30% glucose. CONCLUSIONS:TMPP can regulate the pancreatic islet microcirculation and possess a hypoglycemia effect after glucose infusion through affecting the islet microcirculation.
Entities:
Keywords:
Islet microcirculation; TMPP; The non-radioactive microsphere technique
Authors: Thomas Nyström; Henrik Ortsäter; Zhen Huang; Fan Zhang; Filip J Larsen; Eddie Weitzberg; Jon O Lundberg; Åke Sjöholm Journal: Free Radic Biol Med Date: 2012-06-28 Impact factor: 7.376